Selection of Excipients for the Preparation of Vancomycin-Loaded Poly(D,L-lactide-co-glycolide) Microparticles with Extended Release by Emulsion Spray Drying.

The aim of this study was to relate the composition of the W/O emulsion used as a starting fluid in the spray-drying process to the quality of the dry polymer particles obtained in terms of physical-chemical properties, compatibility and drug release performance. Four W/O emulsions containing vancomycin hydrochloride (VAN), an encapsulating PLGA polymer and Poloxamer® 407, chitosan and/or sorbitan monooleate as stabilisers were spray-dried using an ultrasonic atomising nozzle. The microparticles obtained were micron-sized, with a volume mean diameter between 43.2 ± 0.3 and 64.0 ± 12.6 µm, and spherical with a mostly smooth, non-porous surface and with high drug loading (between 14.5 ± 0.6 and 17.1 ± 1.9% w/w). All formulations showed a prolonged and biphasic VAN release profile, with diffusion being the primary release mechanism. Microparticles prepared from the emulsions with Poloxamer® 407 and sorbitan monooleate released VAN rapidly and completely within one day. The release of VAN from microparticles prepared from the emulsion without additives or with chitosan in the inner aqueous phase was significantly decreased; after four days, a cumulative release of 65% and 61%, respectively, was achieved. Microparticles with encapsulated chitosan had the largest mean particle diameter and the slowest release of VAN.

Use of low-field NMR and rheology to evaluate the microstructure and stability of a poly(d,l-lactide-co-glycolide)-based W/O emulsion to be processed by spray drying.

Drug-loaded emulsions for spray drying should be optimised for their rheological behaviour and stability under operating conditions, as this is essential for achieving the desired physicochemical properties of the final dry product. Our aim was therefore to investigate the structure and stability of a water-in-oil (W/O) emulsion containing vancomycin hydrochloride as the active ingredient in the aqueous phase, poly(d,l-lactide-co-glycolide) as the structural polymer in the dichloromethane-based organic phase, and various stabilisers using low-field nuclear magnetic resonance (LF NMR) and rheological characterisation. Four emulsions were tested, namely-one without stabiliser, one with Poloxamer® 407, one with chitosan and Span™ 80 and one with chitosan only. The theoretical interpretation of the rheological data allowed the determination of the velocity and the shear rate/stress profiles inside the feed path of the W/O emulsion, aspects that are critical for the industrial scale-up of the emulsion drying process. In addition, LF NMR demonstrated that shaking was sufficient to restore the original emulsion structure and that the droplet size of all emulsions was in the range of 1-10 µm, although the emulsion with chitosan had the narrowest droplet size distribution and the higher zero shear viscosity, which accounts for the increased long-term stability due to impeded droplets movement.

Efficacy and Safety of Azelaic Acid Nanocrystal-Loaded In Situ Hydrogel in the Treatment of Acne Vulgaris.

Acne vulgaris is a common, multifactorial, inflammatory skin disease affecting the pilosebaceous unit. Topical therapy is the first choice in the treatment of mild to moderate acne, and azelaic acid (AZA) is one of the most commonly used drugs. The aim of this study was to evaluate the safety and efficacy of a low-dose azelaic acid nanocrystal (AZA-NC) hydrogel in the treatment of mild to moderate facial acne. The study was designed as a double-blind, randomized controlled trial. Patients were randomized to treatment with AZA-NC hydrogel, 10%, or AZA cream, 20%, administered in quantities of approximately 1 g twice daily for 8 weeks. Efficacy of therapy was measured by the number of lesions and safety by the frequency and severity of adverse events. At week 8, the success rate of treatment with AZA-NC hydrogel, 10%, was 36.51% (p < 0.001) versus 30.37% (p < 0.001) with AZA cream. At week 8, treatment with AZA-NC hydrogel, 10%, resulted in a significant reduction in total inflammatory lesions from baseline of 39.15% (p < 0.001) versus 33.76% (p < 0.001) with AZA cream, and a reduction in non-inflammatory lesions from baseline of 34.58% (p < 0.001) versus 27.96% (p < 0.001) with AZA cream, respectively. The adverse event rate was low and mostly mild.

Functional ibuprofen-loaded cationic nanoemulsion: Development and optimization for dry eye disease treatment.

Inflammation plays a key role in dry eye disease (DED) affecting millions of people worldwide. Non-steroidal anti-inflammatory drugs (NSAIDs) can be used topically to act on the inflammatory component of DED, but their limited aqueous solubility raises formulation issues. The aim of this study was development and optimization of functional cationic nanoemulsions (NEs) for DED treatment, as a formulation approach to circumvent solubility problems, prolong drug residence at the ocular surface and stabilize the tear film. Ibuprofen was employed as the model NSAID, chitosan as the cationic agent, and lecithin as the anionic surfactant enabling chitosan incorporation. Moreover, lecithin is a mixture of phospholipids including phosphatidylcholine and phosphatidylethanolamine, two constituents of the natural tear film important for its stability. NEs were characterized in terms of droplet size, polydispersity index, zeta-potential, pH, viscosity, osmolarity, surface tension, entrapment efficiency, stability, sterilizability and in vitro release. NEs mucoadhesive properties were tested rheologically after mixing with mucin dispersion. Biocompatibility was assessed employing 3D HCE-T cell-based model and ex vivo model using porcine corneas. The results of our study pointed out the NE formulation with 0.05% (w/w) chitosan as the lead formulation with physicochemical properties adequate for ophthalmic application, mucoadhesive character and excellent biocompatibility.

Evaluation of stability and in vitro wound healing potential of melatonin loaded (lipid enriched) chitosan based microspheres.

The aim of this study was to evaluate long-term stability and assess the wound healing potential of the innovative melatonin-loaded lipid-enriched hybrid system compared to conventional melatonin-loaded chitosan microspheres. The hybrid system contained nanostructured lipid carrier incorporated in the chitosan matrix, in order to modify melatonin release and alter physicochemical characteristics of the delivery system. Stability testing was performed during a six-month period under two conditions: refrigerated (5 ± 3 °C) and at room temperature (25 ± 2 °C/60 ± 5 % RH). Samples stored at both conditions were analyzed in terms of particle size, zeta potential, moisture content and thermal properties. At the end of testing, drug content was determined in all samples. Dressings wound healing potential was assessed by in vitro scratch test using human skin fibroblast cell line. Although both systems showed good stability characteristics, the addition of lipids in the system has improved its wound healing potential.

Azithromycin-liposomes as a novel approach for localized therapy of cervicovaginal bacterial infections.

BACKGROUND: Efficient localized cervicovaginal antibacterial therapy, enabling the delivery of antibiotic to the site of action at lower doses while escaping systemic drug effects and reducing the risk of developing microbial resistance, is attracting considerable attention. Liposomes have been shown to allow sustained drug release into vaginal mucosa and improve delivery of antibiotics to bacterial cells and biofilms. Azithromycin (AZI), a potent broad-spectrum macrolide antibiotic, has not yet been investigated for localized therapy of cervicovaginal infections, although it is administered orally for the treatment of sexually transmitted diseases. Encapsulation of AZI in liposomes could improve its solubility, antibacterial activity, and allow the prolonged drug release in the cervicovaginal tissue, while avoiding systemic side effects. PURPOSE: The objective of this study was to develop AZI-liposomes and explore their potentials for treating cervicovaginal infections. METHODS: AZI-liposomes that differed in bilayer elasticity/rigidity and surface charge were prepared and evaluated under simulated cervicovaginal conditions to yield optimized liposomes, which were assessed for antibacterial activity against several planktonic and biofilm-forming Escherichia coli strains and intracellular Chlamydia trachomatis, ex vivo AZI vaginal deposition/penetration, and in vitro cytotoxicity toward cervical cells. RESULTS: Negatively charged liposomes with rigid bilayers (CL-3), propylene glycol liposomes (PGL-2) and deformable propylene glycol liposomes (DPGL-2) were efficient against planktonic E. coli ATCC 700928 and K-12. CL-3 was superior for preventing the formation of E. coli ATCC 700928 and K-12 biofilms, with IC50 values (concentrations that inhibit biofilm viability by 50%) up to 8-fold lower than those of the control (free AZI). DPGL-2 was the most promising for eradication of already formed E. coli biofilms and for treating C. trachomatis infections. All AZI-liposomes were biocompatible with cervical cells and improved localization of the drug inside vaginal tissue compared with the control. CONCLUSION: The performed studies confirm the potentials of AZI-liposomes for localized cervicovaginal therapy.

Preparation of in situ hydrogels loaded with azelaic acid nanocrystals and their dermal application performance study.

Azelaic acid (AZA) is a dicarboxylic acid that is topically used in the treatment of acne and rosacea since it possesses antibacterial and keratolytic activity. The primary objective of this study was to develop an AZA nanocrystal suspension. It is expected that improved solubility and dissolution rate will result in advanced biopharmaceutical properties, primarily the dermal bioavailability. Furthermore, a topical nanocrystal AZA-loaded hydrogels composed of Pluronic® F127 and hyaluronic acid mixture that are able to deliver AZA into the stratum corneum and deeper skin layers were considered. This study was conducted in order to: 1) determine the effect of non-ionic Polysorbate 60 on the stabilization and particle size of the AZA nanocrystals, as well as the effect of Pluronic® F127, used as an in situ gelation agent, and hyaluronic acid on the viscoelastic properties and the drug release of composed hydrogels, 2) determine the relationship between the rheological properties of the gels and the penetration of AZA into the stratum corneum. The composed hydrogels revealed pseudoplastic flow behaviour. The increase in Pluronic® F127 concentration induced a domination of elastic over viscous behaviour of the gels. The gel containing 15% of Pluronic® F127, 1% of hyaluronic acid and lyophilised 10% nanocrystal AZA suspension was considered to be an optimal formulation, since it possessed the rheological and drug delivery properties desirable for an in situ gelling platform for dermal application.

Single-Dose Pharmacokinetic Properties and Relative Bioavailability of Different Formulations of Posaconazole Oral Suspension in Healthy Volunteers.

The rate and extent of absorption of drugs belonging to Biopharmaceutics Classification System class II are rate-limited by dissolution and highly dependent on the performance of the formulated product. The purpose of the present study was to investigate the potential impact of a surfactant and the particle size of the active substance on the in vitro drug dissolution profiles and in vivo pharmacokinetics of the poorly soluble drug posaconazole. A comparative physicochemical evaluation was conducted, and 3 formulations of posaconazole oral suspension were tested in various dissolution media compared with the reference product. In addition, a comparative bioavailability study was conducted in healthy volunteers under high-fat fed conditions. Bioequivalence was assessed based on plasma concentrations of the parent drug (posaconazole) measured by a validated high-pressure liquid chromatography-tandem mass spectrometry method. The 90% confidence intervals for Cmax and AUC0-72 least-squares mean T/R ratios of all 3 posaconazole formulations were within the bioequivalence acceptance range of 80.00% to 125.00%. The study was useful in the formulation development process and demonstrated that neither surfactant type nor particle size of the active substance within the studied range affected the extent or rate of absorption of posaconazole under the tested fed conditions.

Azithromycin-loaded liposomes for enhanced topical treatment of methicillin-resistant Staphyloccocus aureus (MRSA) infections.

Antibiotic delivery via liposomal encapsulation represents a promising approach for the efficient topical treatment of skin infections. The present study aimed to investigate the potential of using different types of azithromycin (AZT)-loaded liposomes to locally treat skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) strains. Conventional liposomes (CLs), deformable liposomes (DLs), propylene glycol-containing liposomes (PGLs) and cationic liposomes (CATLs) encapsulating AZT were prepared, and their physical characteristics, drug release profiles, ex vivo skin penetration/deposition abilities, in vitro anti-MRSA activities (planktonic bacteria and biofilm) and cell biocompatibilities were assessed. The (phospho)lipid composition and presence of surfactant or propylene glycol affected the physical characteristics of the liposomes, the release profile of AZT, its deposition inside the skin, as well as in vitro antibacterial efficacy and tolerability with the skin cells. All the liposomes retained AZT inside the skin more efficiently than did the control and were biocompatible with keratinocytes and fibroblasts. CATLs, DLs and PGLs efficiently inhibited MRSA strain growth and were superior to free AZT in preventing biofilm formation, exhibiting minimal inhibitory concentrations and minimal biofilm inhibitory concentrations up to 32-fold lower than those of AZT solution, thus confirming their potential for improved topical treatment of MRSA-caused skin infections.

Development of a Clinically Relevant Dissolution Method for Metaxalone Immediate Release Formulations Based on an IVIVC Model.

PURPOSE: The aim of the present work was to classify metaxalone according to the Biopharmaceutics Classification System (BCS), to develop a clinically relevant dissolution method that can be used to predict the oral absorption of metaxalone and to establish an in vitro-in vivo correlation (IVIVC). METHODS: Solubility of the drug was studied in different pH media and permeability studies were performed using a Caco-2 cell model. The in vitro dissolution and in vivo disposition of metaxalone from 3 different immediate release (IR) tablet formulations were investigated using USP 2 apparatus and a single dose, four-way, crossover bioequivalence study in healthy humans along with an oral solution of the drug, respectively. An IVIVC was established by using a direct, differential based method. RESULTS: Metaxalone has been confirmed as a Class II drug according to BCS. Bioavailability studies performed in humans demonstrated that dissolution was the rate limiting step for bioavailability of the drug and one of the test products had significantly improved bioavailability compared to the marketed product Skelaxin®. An IVIVC model was developed that demonstrated an acceptable internal predictability. CONCLUSION: The IVIVC demonstrated that formulation factors play a significant role in dissolution and absorption of metaxalone. A pH 4.5 dissolution medium containing 0.5% NaCl with 0.2% SLS (USP apparatus 2 at 50 rpm) is clinically relevant to predict bioavailability of the drug and is superior to the USP method in terms of the Quality by Design (QbD) concept.

Biopharmaceutical evaluation of surface active ophthalmic excipients using in vitro and ex vivo corneal models.

The objective of this study was to systematically investigate the effects of surface active ophthalmic excipients on the corneal permeation of ophthalmic drugs using in vitro (HCE-T cell-based model) and ex vivo (freshly excised porcine cornea) models. The permeation of four ophthalmic drugs (i.e., timolol maleate, chloramphenicol, diclofenac sodium and dexamethasone) across in vitro and ex vivo corneal models was evaluated in the absence and presence of four commonly used surface active ophthalmic excipients (i.e., Polysorbate 80, Tyloxapol, Cremophor® EL and Pluronic® F68). The concentration and self-aggregation-dependent effects of surface active ophthalmic excipients on ophthalmic drug permeability were studied from the concentration region where only dissolved monomer molecules of surface active ophthalmic excipients exist, as well as the concentration region in which aggregates of variable size and dispersion are spontaneously formed. Neither the surface active ophthalmic excipients nor the ophthalmic drugs at all concentrations that were tested significantly affected the barrier properties of both corneal models, as assessed by transepithelial electrical resistance (TEER) monitoring during the permeability experiments. The lowest concentration of all investigated surface active ophthalmic excipients did not significantly affect the ophthalmic drug permeability across both of the corneal models that were used. For three ophthalmic drugs (i.e., chloramphenicol, diclofenac sodium and dexamethasone), depressed in vitro and ex vivo permeability were observed in the concentration range of either Polysorbate 80, Tyloxapol, Cremophor® EL or Pluronic® F68, at which self-aggregation is detected. The effect was the most pronounced for Cremophor® EL (1 and 2%, w/V) and was the least pronounced for Pluronic® F68 (1%, w/V). However, all surface active ophthalmic excipients over the entire concentration range that was tested did not significantly affect the in vitro and ex vivo permeability of timolol maleate, which is the most hydrophilic ophthalmic drug that was investigated. The results of the dynamic light scattering measurements point to the association of ophthalmic drugs with self-aggregates of surface active ophthalmic excipients as the potential mechanism of the observed permeability-depressing effect of surface active ophthalmic excipients. A strong and statistically significant correlation was observed between in vitro and ex vivo permeability of ophthalmic drugs in the presence of surface active ophthalmic excipients, which indicates that the observed permeability-altering effects of surface active ophthalmic excipients were comparable and were mediated by the same mechanism in both corneal models.

D-Optimal Design in the Development of Rheologically Improved In Situ Forming Ophthalmic Gel.

In situ forming ophthalmic gels need to be fine tuned considering all the biopharmaceutical challenges of the front of the eye in order to increase drug residence time at the application site resulting in its improved bioavailability and efficacy. The aim of this study was to develop in situ forming ophthalmic poloxamer P407/poloxamer P188/chitosan gel fine tuned in terms of polymer content, temperature of gelation, and viscosity. Minimizing the total polymer content while retaining the advantageous rheological properties has been achieved by means of D-optimal statistical design. The optimal in situ forming gel was selected based on minimal polymer content (P407, P188, and chitosan concentration of 14.2%, 1.7%, and 0.25% w/w, respectively), favorable rheological characteristics, and in vitro resistance to tear dilution. The optimal in situ forming gel was proved to be robust against entrapment of active pharmaceutical ingredients making it a suitable platform for ophthalmic delivery of active pharmaceutical ingredients with diverse physicochemical properties.

An overview of in vitro dissolution/release methods for novel mucosal drug delivery systems.

In vitro dissolution/release tests are an important tool in the drug product development phase as well as in its quality control and the regulatory approval process. Mucosal drug delivery systems are aimed to provide both local and systemic drug action via mucosal surfaces of the body and exhibit significant differences in formulation design, as well as in their physicochemical and release characteristics. Therefore it is not possible to devise a single test system which would be suitable for release testing of such complex dosage forms. This article is aimed to provide a comprehensive review of both compendial and noncompendial methods used for in vitro dissolution/release testing of novel mucosal drug delivery systems aimed for ocular, nasal, oromucosal, vaginal and rectal administration.

HCE-T cell-based permeability model: A well-maintained or a highly variable barrier phenotype?

The most extensively characterized human-derived cell line used in transcorneal permeability studies, in terms of passive transcellular and paracellular transport, transporter expression and metabolic enzymes, is the immortalized human corneal epithelial cell line (HCE-T). The purpose of this study is to describe the changes in the HCE-T barrier phenotype in vitro when valid cultivation conditions, in accordance with the standardized HCE-T cell-based model protocol, were employed. Evaluation of the structural and functional barrier properties revealed two different HCE-T barrier phenotypes, depending on the polycarbonate membrane pore size. Model I (pore size 0.4µm) was characterized by a multilayered HCE-T epithelium at the apical side and a weak barrier function (70-115Ω×cm2), whereas Model II (pore size 3µm) consisted of an apical lipophilic HCE-T monolayer and a basolateral lipophilic monolayer of migrated HCE-T cells that showed improved barrier properties (1700-2600Ω×cm2) compared with Model I. Considering the permeation of ophthalmic compounds and in vitro/ex vivo correlation, Model II was better able to predict transcorneal drug permeation. This study highlights the important aspects of HCE-T barrier phenotype variability that should be continuously monitored in the routine application of HCE-T cell-based models across both academic and pharmaceutical industry research laboratories.

Melatonin-loaded chitosan/Pluronic® F127 microspheres as in situ forming hydrogel: An innovative antimicrobial wound dressing.

The aim of this study was to develop melatonin-loaded chitosan based microspheres as dry powder formulation suitable for wound dressing, rapidly forming hydrogel in contact with wound exudate. Microspheres were produced by spray-drying method. Fractional factorial design was employed to elucidate the effect of formulation and process parameters (feed flow rate, inlet air temperature, chitosan concentration, chitosan/melatonin ratio and chitosan/Pluronic® F127 ratio) on the product characteristics related to process applicability (production yield, entrapment efficiency and product moisture content) and microsphere performance in biological environment (microsphere mean diameter and surface charge). Appropriate formulation and process parameters for the establishment of efficient drying process resulting in fine-tuned chitosan and chitosan/Pluronic® F127 microspheres (efficient melatonin encapsulation, small diameter positive surface charge and low moisture content) were identified. Microspheres were characterized by appropriate flowability and high rate and extent of fluid uptake. Incorporation of Pluronic® F127 in microsphere matrix resulted in high melatonin amorphization and consequent higher melatonin release rate. Entrapment of melatonin in chitosan/Pluronic® F127 microspheres has potentiated chitosan antimicrobial activity against Staphylococcus aureus and five clinical isolates S. aureus MRSA strains. Microspheres were shown to be biocompatible with skin keratinocytes and fibroblasts at concentrations relevant for antimicrobial activity against planktonic bacteria.

Nanoparticle-mediated interplay of chitosan and melatonin for improved wound epithelialisation.

Herein, we propose an innovative approach to improving wound healing. Our strategy is to deliver melatonin locally at the wound site by means of lecithin/chitosan nanoparticles. We used four types of chitosan that differed in terms of molecular weight and/or deacetylation degree. Melatonin encapsulation efficiency, nanoparticle size, zeta potential, biocompatibility and in vitro drug release were studied as a function of the type of chitosan used in preparation. The nanoparticles were evaluated in terms of their potential to promote wound epithelialisation via an in vitro scratch assay using a human keratinocyte (HaCaT) monolayer. The model wounds were treated with nanoparticle suspensions at a chitosan concentration of 5µgml(-1), which was based on preceding cell biocompatibility studies. Nanoparticles prepared with different types of chitosan showed similar effect on the keratinocyte proliferation/migration. Nanoparticle-mediated interplay of chitosan and melatonin was shown to be crucial for improved wound epithelialisation.

Evaluation of cationic nanosystems with melatonin using an eye-related bioavailability prediction model.

In this study, two types of nanosystems, namely lecithin/chitosan nanoparticles and Pluronic® F127/chitosan micelles, have been prepared and evaluated for their potential for the ocular delivery of melatonin, which is known to exert an ocular hypotensive effect. The melatonin content, particle size, zeta potential and in vitro drug release properties were studied as a function of the presence of chitosan in the nanosystem. Lecithin/chitosan nanoparticles were evaluated in terms of the mucoadhesive properties by a newly established method based on HCE-T cells, also used in in vitro biocompatibility and permeability studies. Lecithin/chitosan nanoparticles were significantly larger than the corresponding F127/chitosan micelles (mean diameter of 241.8 vs. 20.7nm, respectively) and characterised by a higher surface charge (22.7 vs. 4.3mV, respectively). The HCE-T cell viability assay did not show significant toxic effects of nanosystems investigated at the (relevant) chitosan concentration tested. The permeability study results confirmed the permeation enhancing effect of F127, which was hindered in the presence of chitosan. Lecithin/chitosan nanoparticles were characterised by prominent mucoadhesive properties and prolonged melatonin release, which was shown to control melatonin permeation across an in vitro corneal epithelial model. Such properties demonstrate the potential for nanoparticles to provide an extended pre-corneal residence time of melatonin, ensuring higher eye-related bioavailability and extended intraocular pressure reduction compared to melatonin in both aqueous and micelle solutions.

In vitro skin models as a tool in optimization of drug formulation.

(Trans)dermal drug therapy is gaining increasing importance in the modern drug development. To fully utilize the potential of this route, it is important to optimize the delivery of active ingredient/drug into/through the skin. The optimal carrier/vehicle can enhance the desired outcome of the therapy therefore the optimization of skin formulations is often included in the early stages of the product development. A rational approach in designing and optimizing skin formulations requires well-defined skin models, able to identify and evaluate the intrinsic properties of the formulation. Most of the current optimization relies on the use of suitable ex vivo animal/human models. However, increasing restrictions in use and handling of animals and human skin stimulated the search for suitable artificial skin models. This review attempts to provide an unbiased overview of the most commonly used models, with emphasis on their limitations and advantages. The choice of the most applicable in vitro model for the particular purpose should be based on the interplay between the availability, easiness of the use, cost and the respective limitations.

Development and validation of an in vitro release method for topical particulate delivery systems.

The aim of this study was to develop an in vitro release method for topical particulate delivery systems using the immersion cell in combination with paddle dissolution apparatus. Chitosan- and methacrylate-based microparticles with mupirocin were prepared and used as model topical delivery systems for method development. Diffusion of the drug occurred across a mixed cellulose ester membrane, which demonstrated low drug adsorption and low diffusional resistance. After an initial lag phase the amount of drug released became proportional to the square root of time. The method was discriminative toward differences in formulation, as well as toward differences in drug concentration inside the sample compartment. The method was further used to confirm sameness between batches of the same composition prepared by the same process. Variations in paddle rotation speed (25 rpm, 50 rpm, 100 rpm), paddle height (1cm, 2.5 cm) and volume of release medium (100ml, 200 ml) did not significantly alter the release rates. The method of analysis was validated according to ICH guidelines. Currently there are no compendial or standard methods and apparatuses for in vitro release testing of topical microparticles. The developed method can be a useful guide in formulation development of such delivery systems.

Elastic liposomes-in-vehicle formulations destined for skin therapy: the synergy between type of liposomes and vehicle.

OBJECTIVE: The present study is focused on optimization of elastic liposomes-in-vehicle formulations in respect to drug release and formulation properties. By combining penetration potential of elastic liposomes containing high ratio of entrapped drug and physicochemical properties of vehicles, both affecting the release and texture properties, optimal formulation could be achieved. MATERIALS AND METHODS: Deformable, propylene glycol-containing or conventional liposomes with hydrophilic model drug (diclofenac sodium) were incorporated into the following vehicles appropriate for skin application: a hydrogel, a cream base and derma membrane structure base cream (DMS base). Each formulation was assessed for in vitro drug release and mechanical properties. RESULTS AND DISCUSSION: The composition and type of both liposomes and the vehicle affected the rate and amount of the released drug. The cream base exhibited the slowest release, followed by the hydrogel and DMS base. Similar release profiles were achieved with both types of elastic vesicles (deformable and propylene glycol liposomes); the slowest release was observed for conventional liposomes, regardless of the vehicle used. The drug release profiles from different liposomes-in-vehicle formulations were in agreement with the physicochemical properties of the formulations. All of the liposomes were found to be compatible with the hydrogel preserving its original textures, whereas a significant decrease in all texture parameters was observed for liposomes-in-DMS base, regardless of liposome type. CONCLUSION: Propylene glycol liposomes-in-hydrogel is considered as the optimal formulation for improving skin delivery of hydrophilic drug. Further investigations involving in vivo animal studies are necessary to confirm its applicability in skin therapy.